FI70364B - TILLSATSFODER INNEHAOLLANDE EN KOMBINATION AV KITASAMYCIN OCH N- (2-HYDROXYETHYL) -3-METHYL-2-QUINOXALINCARBOXYLSYRAMIDE-1,4-DI-N-OXIDE - Google Patents

Abstract

1. Active compound combination consisting of kitasamycin and 2-methyl-3-carboxamidoquinoxaline- -1,4-di-N-oxides of the general formula I see diagramm : EP0073390,P9,F2 wherein R**1 represents hydrogen, lower alkyl, lower alkoxy radicals and chlorine, R**2 represents hydrogen or a straight-chain or branched alkyl radical which is optionally substituted by a hydroxyl, lower alkoxy, carboalkoxy, mono- or dialkylamino radical, R**3 can represent hydrogen and wherein R**3 furthermore can be identical to or different from R**2 and in the case where R**2 is hydrogen R**3 can also represent the cyclohexyl radical and wherein in the case where R**2 and R**3 denote alkyl these radicals, together with the amide nitrogen atom, can be a constituent of a 5- or 6-membered heterocyclic ring system.

Description

1 70364

The invention relates to a supplementary feed containing chitamycin and N- (2-hydroxyethyl) -N-2-hydroxy-ethyl-2-quinoxalinicarboxylic acid amide-1,4-di-N-oxide. ) -3-methyl-2-quinoxalinecarboxylic acid amide-1,4-di-N-oxide and which can be used to promote the growth of animals and improve their food utilization.

It is known that citasamycin (see U.S. Patent 3,535,309; The Merck Index. 9th Edition) has antimicrobial activity and is also used as a food additive. The 2-methyl-3-carboxylic acid amidinoxaline-1,4-di-N-oxide class certainly includes the most potent animal growth promoters (see DE 1 670 935), such as N- (2-hydroxyethyl) -3 -methyl-3-quinoxalinecarboxylic acid amide-1,4-di-N-oxide (Olaquindox).

It has now been found that chitamycin and 2-methyl-3-20 carboxylic acid amidinoxaline-1,4-di-N-oxides, in particular N- (2-hydroxyethyl) -3-methyl-2-quinoxalinecarboxylic acid amide-1,4-di- * The combination of N-oxide results in an increased growth-promoting and nutritional-enhancing effect in animals.

The invention therefore relates to a supplementary feed comprising, in combination as active ingredients, chitamycin and N- (2-hydroxyethyl) -3-methyl-2-quinoxalinecarboxylic acid amide-1,4-N-oxide having the formula

O

'h N ^^ CH.

3

O

The supplementary feed according to the invention can be used to promote the growth of animals and to improve their nutritional use.

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The supplementary feed according to the invention preferably contains chitazamycin and a quinoxaline di-N-oxide derivative in a ratio ranging from 10: 1 to 1:10.

The preparation of quinoxaline-1,4-di-N-oxides as well as citasamycin-5 is known from the literature initially mentioned. By chitamamycin in the context of the invention is meant both a mixture of biologically active components and also isolated individual components and mixtures of two or more individual components.

The supplementary feed according to the invention can be used in all fields of animal husbandry in the case of healthy and diseased animals as a growth-promoting and accelerating substance and as a food-improving substance.

The effect of the combination of active substances used in the feed according to the invention is then somewhat independent of the animal species and the sex of the animals. The complementary feeds according to the invention are particularly valuable in the rearing and keeping of young animals and animals for slaughter. As animals in which the supplementary compound compositions according to the invention can be used to promote and accelerate their growth and to improve their nutritional utilization, for example the following useful and pet animals: homogenous, such as cattle, pigs, horses, sheep, goats, cats, dogs, rabbits, fur animals, e.g.

25 nerds and chinchillas, poultry, e.g., chickens, geese, ducks, turkeys, pigeons, parrots, and canaries, and heather, such as fish, e.g., carp and reptiles, e.g., snakes.

The amount of active ingredient combination used in accordance with the invention that is administered to animals to achieve the desired effect can vary widely due to the beneficial properties of the active ingredients. It is preferably about 5 to 500, especially 10 to 100 mg per kilogram of body weight per day. Administration can be continued for a few hours or days to a few years. The appropriate amount of active substances as well as the appropriate duration of administration depend in particular on the species, age, sex, state of health and nature of the animals and are readily apparent to one skilled in the art.

The combinations of active ingredients used according to the invention are administered to the animals by conventional methods. The route of administration depends in particular on the species, the behavior and the state of health of the animals. Thus, administration may be once or several times a day, at regular or irregular intervals, orally or parenterally. For convenience, oral administration, especially when eating and / or drinking animals, is preferred in most cases.

The combinations of active ingredients used according to the invention can be administered as a mixture of ingredients alone or in formulated form, i.e. in admixture with various non-toxic inert carriers, e.g. in admixture with carriers or in formulations customary in the preparation of foodstuffs.

They are administered in a suitable form, optionally in combination with pharmaceutically active substances, mineral salts, trace elements, vitamins, proteins, fats, colors and / or flavorings.

Oral administration with food and / or drinking water is recommended, with combinations of active ingredients being added to all or part of the food and / or drinking water whenever necessary.

The active compound combinations used according to the invention are added to food and / or drinking water by conventional methods, simply by mixing as a simple mixture, preferably in finely divided form, or in formulated form with edible non-toxic carriers, optionally as a premix or concentrate.

The food and / or drinking water may contain the combinations of active ingredients according to the invention, for example in concentrations (w / w) of about 5 to 500 ppm, in particular 0 to 100 ppm.

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The most preferred concentration of active ingredients in food and / or drinking water depends in particular on the amount of food and / or drinking water consumed by the animals and can be easily determined by one skilled in the art.

5 The quality of the food and its composition are irrelevant in this context. All commonly used or special nutritional compositions can be used, which preferably contain the usual amount of energy-containing substances and building materials, including vitamins and minerals, necessary for a balanced diet. The diet may consist of, for example, plant materials, e.g. hay, beets, grains and their by-products, materials of animal origin, e.g. meat, fats, bone meal, fish products, vitamins, e.g.

15 Vitamin A, Group D and Group B vitamins, proteins, amino acids such as DL-methionine, and inorganic substances such as lime and common salt.

Nutrient concentrates contain the combinations of active ingredients used according to the invention in addition to edible substances, e.g. rye flour, corn flour, soybean meal or lime, optionally with other nutrients and building materials as well as proteins, mineral salts and vitamins. They can be prepared by conventional mixing methods.

Advantageously, the combination of active ingredients in premixes and nutritional concentrates can possibly also be protected by suitable substances covering their surface, e.g. non-toxic waxes or gelatin, from the effects of air, light and / or moisture.

Example of a composition for a broiler rearing diet comprising a combination of active ingredients to be used according to the invention: 200 g wheat, 340 g maize, 361 g soy flour, 60 g beef fat, 15 g dicalcium phosphate, 10 g calcium carbonate, 4 g iodine cooking salt, 7.5 g -miner mixture, 2.5 g of the premix of active ingredients, after thorough mixing, yields 1 kg of food.

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The vitamin-mineral mixture contains: 600 IU vitamin A, 100 IU vitamin D 1, 10 mg vitamin E, 1 mg vitamin K 2, 3 mg riboflavin, 2 mg pyridoxine, 20 mg vitamin B , 5 mg of calcium pantothenate-5, 30 mg of nicotinic acid, 200 mg of choline chloride, 200 mg of MnSO 4 .7H 2 O, 140 mg of ZnSO 4 .7H 2 O, 100 mg of FeSO 2 .7H 2 O and 20 mg of CuSO 4 .5H 2 O: a.

The premix of active ingredients contains the desired amount, e.g. 100 mg, of the combinations of active ingredients used according to the invention, in addition to 1 g of DL-methionine and enough soybean meal to form 2.5 g of premix.

Example of a composition for a pig feed containing a combination of active ingredients to be used according to the invention: 630 g of feed grain flour (consisting of 200 g of maize, 150 g of barley, 150 g of oats and 130 g of wheat flour), 80 g of fishmeal, 60 g of soybean meal, 60 g of ta-pioca meal, 38 g of brewer's yeast, 50 g of a mixture of 20 mineral minerals suitable for pigs (composition e.g. After thorough mixing, 2 g of a premix of active ingredients (for example, the same composition as in a chicken-25 diet) results in 1 kg of food.

The indicated nutritional compositions are preferably adapted for the rearing and fattening of broilers or pigs, but may also be used in the same or a similar composition for the rearing and fattening of other animals.

Using the supplementary feed according to the invention, a few feeding experiments were performed.

They gave the following results.

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Example 1 a) Characteristics and nutrition of animals ai) Piglets 5 a2) Number 30 a3) Breeding of large white breeds a4) Sex male a5) Age about 8-14 weeks -j ^ q a6) Weight 17.5 - 45 kg a7 ) Good condition

Crude protein (min.) 17.0%

Crude fat 2.5

Fiber content 5.0% 15 Salt 0.5%

Urea (max.) 0.0%

Fluorine (max.) 0.01%

Lysine 0.832%

Methionine 0.249% 20 Threonine 0.494%

Isoleucine 0.564%

Methionine + cysteine 0.522%

Tryptophan 0.209%

Biotin 0.108% 25

Choline 0.110%

Calcium 1,035%

Phosphorus 0.790%

Ingredients: 30 Wheat, barley, millet, bran, meat meal, soybean meal, cottonseed meal, sunflower meal and, lysine, salt, limestone, 2RO, MnO, copper and iron sulphate, E-, E-, potassium iodide, A, iodide, Vitamin B2, niacin, pantothenic acid.

7 70364 b) Treatment of animals

The animals were treated in 5 groups. The initial weight in each group was the same, ppm 5 bl) Olaquindox 50 b2) Chitosanamine 50 b3) Olaquindox + chitamycin 25:25 b4) Olaquindox + chitamycin 12.5: 12.5 b5) Comparison (without active ingredients 10) o) Solution

The piglets were weighed daily. Daily weight gain and dietary intake were determined. The weekly weighing result and the food consumption of each animal were memorized.

d) Results (weight gain g / day)

Concentration (ppm) Average daily weight gain (g / day) 9n dl) 50 593 d2) 50 562 d3) 25:25 626 d4) 12.5: 12.5 560 d5) comparison 537 25 The synergistic effect on weight gain is significant.

e) Results (food utilization)

Concentration (ppm) Average food intake ratio (g / g) 30 el) 50 2.52 e2) 50 2.64 e3) 25:25 2.44 e4) 12.5: 12.5 2.66 e5) comparison 2 .72 35 The synergistic effect on food intake is significant.

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Example 2 a) Animal characteristics and nutrition ai) Piglets a2) Number 84 5 a3) Sex of both a4) Breeding of large white breeds a5) Age 5 weeks a6) Weight 7-75 kg • ^ q a7) Condition good a8) Nutrition 18% crude protein at the beginning of kg / ton

Wheat 730

Meat flour 100

Soy flour 120

Sunflower meal 30

Mineral-vitamin premix 10

Vegetable oil 10 20 16% crude protein at the end

Wheat 804

Meat flour 125

Sunflower meal 60

Mineral-vitamin mixture 10 25 Methionine 1 b) Treatment of animals dosage ppm up to 40 kg up to 75 kg bl) Olaquindox 100 25 b2) Chitosanamycin 55 11 b3) Olaquindox + chitosanamine 25:22 25:11 ^ b4) Comparison c) Solution

Piglets were weighed at the beginning of the experiment and at weekly or 14-day intervals until the end of the experiment.

Food intake and mortality were recorded daily.

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At the end of the experiment, the thickness of the back fat was measured with an ultrasonic device and corrected to correspond to a live weight of 75 kg.

(d) Results (weight gain g / day)

Chassis to 40 kg from 40 kg to the end From the beginning to the end dl) 499 641 573 d2) 508 574 522 d3) 517 624 568

10 d4) 460 593 53I

e) Results (food use g / q)

Chassis to 40 kg from 40 kg to 75 kg From start to finish 15 el) 2.30 3.10 2.74 e2) 2.28 3.17 2.74 e3) 2.15 2.80 2.48 e4 ) 2.41 3.18 2.81 2Q f) Results (back fat thickness)

Back fat (mm) fl) 21.3 f2) 20.3 f3) 20.7 25 f4) 21.6

Example 2 also clearly shows the superiority of the imimi combination preparation.

Claims (2)

10 703 6 4 Complementary feed for use in improving the growth rate and dietary utilization of animals, characterized in that it contains a combination of active ingredients consisting of citasamycin and CO-NH-CH-CH-OH! N- 1 22 10 155 N- (2-hydroxyethyl) -3-methyl-2-quinoxalinecarboxylic acid amide-1,4-di-N-oxide in a ratio ranging from 1:10 to 10: 1. Complementary feed according to Claim 1, characterized in that it contains chitazamycin and N- (2-hydroxyethyl) -3-methyl-2-quinoxalinecarboxylic acid amide-1,4-di-N-oxide in a ratio of 1: 1.